A novel model for the induction of postnatal murine hip deformity

Abstract

Acetabular dysplasia is a recognized cause of hip osteoarthritis (OA). A paucity of animal models exists to investigate structural and functional changes that mediate morphology of the dysplastic hip and drive the subsequent arthritic cascade. Utilizing a novel murine model, this study investigated the role of surgically-induced unilateral instability of the postnatal hip on the initiation and progression of acetabular dysplasia and impingement up to 8-weeks post-injury. Specifically, C57BL6 mice were used to develop titrated levels of hip instability (mild, moderate, severe, and femoral head removal) at 3-weeks of age, a critical time for hip maturation. Joint shape, acetabular coverage, histomorphology, immunohistochemistry, and statistical shape modeling were used to assess overall quality of joint health and three-dimensional hip shape following 8 weeks of titrated destabilization. This titrated approach included mild, moderate, severe, and complete instability via surgical destabilization of the murine hip. Acetabular coverage was reduced following severe, but not moderate, instability. Moderate instability induced lateralization of the femoral head without dislocation, whereas severe instability led to complete dislocation and formation of pseudoacetabula. Mild instability did not result in statistically significant morphological changes to the hip. Complete destabilization via femoral head removal led to reduced joint space volume and reduced bone volume ratio in the remnant proximal femur. Collectively, these results support the notion that hip instability, driven by loss of function, leads to morphometric changes in the maturing mouse hip. This model could be useful for future studies investigating the mechanical and cellular adaptations to hip instability during maturation.

A Murine Model of Abductor Insufficiency Accelerates the Development of Hip Osteoarthritis

“…However, it is not clear whether such a progressive and destructive OA phenotype is representative of chronic hip OA in humans 22 . In another study, various degrees of hip instability ranging from mild, moderate, severe to femoral head resection were surgically induced in mice at weaning (3-week-old neonatal pups) 16 . Their data suggest that hip instability induced by loss-of-function of soft connective tissue led to morphometric changes in the growing mouse hip.…”

“…With the growth in clinical evidence indicating an association between abductor insufficiency and the development of hip OA, it is essential to develop a reproducible small animal model that allows scientists to study the pathogenesis of this linked disease process 5,6 . To date, however, only a few rodent hip OA models have been established and can be generally categorized into either chemically-induced or surgically-induced OA 16,22 . Intra-articular injection of monosodium Iodoacetate (a chondrocyte glycolytic inhibitor) exhibited rapid hip OA development compared to controls within 14 days in a rat model.…”

“…Furthermore, there is a paucity of literature on murine hip injury models 16 . The purpose of the present study, therefore, was to establish a novel murine model of hip OA induced by abductor injury and determine whether an association exists between abductor insufficiency and hip OA onset and progression.…”

“…Despite these benefits, large animals are not amenable to the power of genetic modification to better define the cellular and molecular etiology of pathogenesis, as can be conducted in mice 15 . Furthermore, there is a paucity of literature on murine hip injury models 16 . The purpose of the present study, therefore, was to establish a novel murine model of hip OA induced by abductor injury and determine whether an association exists between abductor insufficiency and hip OA onset and progression.…”

A Novel Model of Hip Femoroacetabular Impingement in Immature Rabbits Reproduces the Distinctive Head-Neck Cam Deformity

“…To date, there have been limited animal models of hip OA secondary to FAI. Recently, an article published by Killian et al 15 reported on a murine model of hip instability. Up to now, there has been only 1 reported large animal model of experimentally induced hip FAI in sheep 28,34 in which a deformity was created via intertrochanteric varus osteotomy.…”